Stress induced heatstroke occurs during strenuous exercise in a hot environment. Apart from the necessary environmental conditions, and the lack of acclimatization to them, many other factors can contribute to its etiology, including the use of prescription drugs and drug abuse. The majority of reports of fatal cases of stress related heatstroke have involved military recruits undergoing training of deployment in tropical regions or athletes during training for various events. Among American athletes heatstroke is a leading cause of death, second only to head and spinal injuries. The illicit use of cocaine by all strata of society has reached epidemic proportions and the young athlete, both amateur and professional, is a major participant in this problem. This research is designed to determine if abuse of cocaine constitutes a risk factor in the pathogenesis of stress (exertion) induced heatstroke. It will also investigate whether adrenergic compounds may be useful in preventing or treating heatstroke related to use of the drug. The role of prior physical conditioning on the severity of the ensuing core temperature changes will be investigated. The laboratory rat will be used as model of the human condition. Changes in core temperature will be measured, at ambient temperatures of 22 degrees C can 35 degrees C, with the animals either at rest, or undergoing mild and more severe exercise on a treadmill. Behavioral studies will establish if cocaine causes a shift in the thermoregulatory set point or activates directly peripheral heat loss and gain systems. Cocaine will also be injected directly into the rostral hypothalamus to establish if its locus of action is on the thermoregulatory centers. Drugs which modify central adrenergic function (prazosin and clonidine) will be tested for their ability to prevent the onset of hyperthermia and to ameliorate established hyperthermia. The mortality rate from heatstroke may exceed 30%; the victim succumbs rapidly unless the core temperature is quickly lowered. If this study confirms that cocaine contributes to heatstroke, an awareness of its potential would help in assuring prompt and appropriate management of the victims; and the possible therapeutic value of the adrenoreceptor drugs would aid in treatment.